TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22788	68587;68588;68589	chr2:178578153;178578152;178578151	chr2:179442880;179442879;179442878
N2AB	21147	63664;63665;63666	chr2:178578153;178578152;178578151	chr2:179442880;179442879;179442878
N2A	20220	60883;60884;60885	chr2:178578153;178578152;178578151	chr2:179442880;179442879;179442878
N2B	13723	41392;41393;41394	chr2:178578153;178578152;178578151	chr2:179442880;179442879;179442878
Novex-1	13848	41767;41768;41769	chr2:178578153;178578152;178578151	chr2:179442880;179442879;179442878
Novex-2	13915	41968;41969;41970	chr2:178578153;178578152;178578151	chr2:179442880;179442879;179442878
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-53
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0568
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
L/P	rs745626806	-0.116	0.975	N	0.659	0.52	0.712016079665	gnomAD-2.1.1	4.44E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.8E-05	0
L/P	rs745626806	-0.116	0.975	N	0.659	0.52	0.712016079665	gnomAD-4.0.0	1.84846E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.33942E-05	0	1.65722E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
L/A	0.7135	likely_pathogenic	0.7002	pathogenic	-0.475	Destabilizing	0.547	D	0.56	neutral	None	None	None	None	I
L/C	0.917	likely_pathogenic	0.8859	pathogenic	-0.822	Destabilizing	0.985	D	0.599	neutral	None	None	None	None	I
L/D	0.9708	likely_pathogenic	0.9725	pathogenic	-0.052	Destabilizing	0.981	D	0.664	neutral	None	None	None	None	I
L/E	0.9066	likely_pathogenic	0.9032	pathogenic	-0.135	Destabilizing	0.945	D	0.661	neutral	None	None	None	None	I
L/F	0.495	ambiguous	0.4267	ambiguous	-0.594	Destabilizing	0.864	D	0.574	neutral	N	0.495162012	None	None	I
L/G	0.9164	likely_pathogenic	0.9076	pathogenic	-0.574	Destabilizing	0.945	D	0.661	neutral	None	None	None	None	I
L/H	0.7684	likely_pathogenic	0.7154	pathogenic	0.094	Stabilizing	0.993	D	0.675	prob.neutral	N	0.506032366	None	None	I
L/I	0.1375	likely_benign	0.121	benign	-0.331	Destabilizing	0.006	N	0.401	neutral	N	0.393267008	None	None	I
L/K	0.7996	likely_pathogenic	0.7841	pathogenic	-0.31	Destabilizing	0.945	D	0.615	neutral	None	None	None	None	I
L/M	0.2336	likely_benign	0.1955	benign	-0.624	Destabilizing	0.894	D	0.584	neutral	None	None	None	None	I
L/N	0.8187	likely_pathogenic	0.8045	pathogenic	-0.209	Destabilizing	0.981	D	0.654	neutral	None	None	None	None	I
L/P	0.7429	likely_pathogenic	0.7108	pathogenic	-0.352	Destabilizing	0.975	D	0.659	neutral	N	0.454987471	None	None	I
L/Q	0.6827	likely_pathogenic	0.6335	pathogenic	-0.351	Destabilizing	0.981	D	0.616	neutral	None	None	None	None	I
L/R	0.734	likely_pathogenic	0.6884	pathogenic	0.116	Stabilizing	0.928	D	0.621	neutral	N	0.472015793	None	None	I
L/S	0.8329	likely_pathogenic	0.8065	pathogenic	-0.625	Destabilizing	0.894	D	0.625	neutral	None	None	None	None	I
L/T	0.7065	likely_pathogenic	0.7027	pathogenic	-0.605	Destabilizing	0.894	D	0.531	neutral	None	None	None	None	I
L/V	0.2167	likely_benign	0.1881	benign	-0.352	Destabilizing	0.006	N	0.409	neutral	N	0.470322282	None	None	I
L/W	0.7539	likely_pathogenic	0.69	pathogenic	-0.61	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	I
L/Y	0.7648	likely_pathogenic	0.7323	pathogenic	-0.387	Destabilizing	0.945	D	0.582	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.